Exposure of the airways to carbonaceous nanoparticles can contribute to the development of immune diseases both via the aggravation of the allergic immune response in sensitized individuals and by adjuvant mechanisms during the sensitization against allergens. The cellular and molecular mechanisms involved in these adverse pathways are not completely understood. We recently described that the reduction of carbon nanoparticle-induced lung inflammation by the application of the compatible solute ectoine reduced the aggravation of the allergic response in an animal system. In the current study we investigated the influence of carbon nanoparticles on the sensitization of animals to ovalbumin via the airways. Ectoine was used as a preventive strategy against nanoparticle-induced neutrophilic lung inflammation. Balb/c mice were repetitively exposed to the antigen ovalbumin after induction of airway inflammation by carbon nanoparticles, either in the presence or in the absence of ectoine. Allergic sensitization was monitored by measurement of immunoglobulin levels and immune responses in lung and lung draining lymph nodes after challenge. Furthermore the role of dendritic cells in the effect of carbon nanoparticles was studied in vivo in the lymph nodes but also in vitro using bone marrow derived dendritic cells. Animals exposed to antigen in the presence of carbon nanoparticles showed increased effects with respect to ovalbumin sensitization, to the allergic airway inflammation after challenge, and to the specific TH2 response in the lymph nodes. The presence of ectoine during the sensitization significantly reduced these parameters. The number of antigen-loaded dendritic cells in the draining lymph nodes was identified as a possible cause for the adjuvant effect of the nanoparticles. In vitro assays indicate that the direct interaction of the particles with dendritic cells is not able to trigger CCR7 expression, while this endpoint is achieved by lung lavage fluid from nanoparticle-exposed animals. Using the intervention strategy of applying ectoine into the airways of animals we were able to demonstrate the relevance of neutrophilic lung inflammation for the adjuvant effect of carbon nanoparticles on allergic sensitization.

中文翻译：

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预防碳纳米颗粒诱导的肺部炎症可降低小鼠模型中的抗原特异性致敏作用和随后的过敏反应。

气道暴露于碳质纳米颗粒可通过加剧致敏个体的变应性免疫应答以及在变应原致敏过程中的辅助机制而促进免疫疾病的发展。这些不良途径中涉及的细胞和分子机制尚不完全清楚。我们最近描述了通过应用相容性溶质外啡减少碳纳米颗粒诱导的肺部炎症可减少动物系统中过敏反应的加剧。在当前的研究中，我们研究了碳纳米颗粒对动物通过气道对卵白蛋白致敏性的影响。Ectoine被用作预防纳米颗粒诱导的嗜中性肺炎的策略。在存在或不存在植物素的情况下，碳纳米颗粒诱导气道炎症后，Balb / c小鼠反复暴露于卵清蛋白抗原。通过检测激发后肺和肺引流淋巴结中的免疫球蛋白水平和免疫应答来监测过敏性致敏。此外，在体内淋巴结中研究了树突状细胞在碳纳米颗粒作用中的作用，但在体外也使用骨髓衍生的树突状细胞进行了研究。在碳纳米颗粒存在下暴露于抗原的动物对卵清蛋白致敏，激发后对过敏性气道炎症以及淋巴结中特定的TH2反应均表现出增强的作用。敏化过程中油酸的存在显着降低了这些参数。引流淋巴结中负载抗原的树突状细胞的数量被确定为纳米颗粒佐剂作用的可能原因。体外试验表明，颗粒与树突状细胞的直接相互作用不能触发CCR7表达，而这一终点是通过暴露于纳米颗粒动物的肺灌洗液来实现的。使用将ectoine应用于动物气道的干预策略，我们能够证明嗜中性肺部炎症与碳纳米颗粒对变态反应致敏的辅助作用的相关性。体外测定表明，颗粒与树突状细胞的直接相互作用不能触发CCR7表达，而这一终点是通过暴露于纳米颗粒动物的肺灌洗液来实现的。使用将ectoine应用于动物气道的干预策略，我们能够证明嗜中性肺部炎症与碳纳米颗粒对变态反应致敏的辅助作用的相关性。体外测定表明，颗粒与树突状细胞的直接相互作用不能触发CCR7表达，而这一终点是通过暴露于纳米颗粒动物的肺灌洗液来实现的。使用将ectoine应用于动物气道的干预策略，我们能够证明嗜中性肺部炎症与碳纳米颗粒对过敏性致敏的辅助作用的相关性。